- Affiliate Professor, Global Health
Center for Infectious Disease Research
307 Westlake Avenue N. Suite 500
Seattle, WA 98109
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Dr. Smith's lab studies the malaria parasite Plasmodium falciparum. The goal of the lab is to understand pathogenic disease mechanisms and to characterize critical parasite-host binding interactions. We use this knowledge to design vaccine or disease interventions. A major research focus in the laboratory is antigenic variation and cytoadhesion of P. falciparum infected erythrocytes to the endothelial lining of blood vessels. By sequestering from blood circulation, infected erythrocytes avoid spleen dependent killing mechanisms, but this phenomenon can lead to severe disease complications when infected erythrocytes accumulate in brain or placental blood vessels. We are interested in how the parasite adhesion ligands are trafficked to the surface of infected erythrocyte and how they determine parasite binding tropism. We recently discovered that a distinct subset of parasite ligands is associated with the deadly malaria complication, cerebral malaria. We are following up on these findings to identify the host receptor binding partners and to characterize cerebral malaria disease mechanisms. In addition, the Smith lab is interested in vaccine design approaches to inhibit parasite invasion of host cells.
- PhD (Washington University)
- BA (Macalester College)
- Host-pathogen Interactions
- Infectious Diseases
Avril M, Tripathi AK, Andisi C, Janes JH, Brazier J, Soma V, Sullivan DJ Jr, Bull PC, Stins MF, and Smith JD. (2012) A restricted subset of var genes is associated with adherence of Plasmodium falciparum infected erythrocytes to brain endothelial cells. Proc. Natl. Acad. Sci. USA . 109:E1782-90. PMCID: PMC3387091
Turner L, Lavstsen T, Berger SS, Wang CW, Petersen JEV, Avril M, Brazier AJ, Freeth J, Jespersen JS, Nielsen MA, Magistrado P, Lusingu J, Smith JD, Higgins MK, and Theander TG. (2013) Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature 498:502-5. PMCID:PMC3870021
Avril M, Brazier AJ, Melcher M and Smith JD. (2013) DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells. Plos Pathogens 9:e1003430. PMCID: PMC3694856.
Kessler A, Dankwa S, Bernabeu M, Harawa V, Danziger SA, Duffy F, Kampondeni SD, Potchen MJ, Dambrauskas N, Vigdorovich V, Oliver BG, Hochman SE, Mowrey WB, MacCormick IJC, Mandala WL, Rogerson SJ, Sather DN, Aitchison JD, Taylor TE, Seydel KB, Smith JD, and K Kim. (2017) Linking EPCR-binding PfEMP1 to brain swelling in pediatric cerebral malaria. Cell Host & Microbe. 22:601-614.
Bernabeu, M., Danziger SA, Avril M, Vaz M, Babar PH, Brazier AJ, Herricks T, Maki JN, Pereira L, Mascarenhas A, Gomes E, Chery L, Aitchison JD, Rathod PK, JD Smith. (2016) Severe adult malaria is associated with specific PfEMP1 adhesion types and high parasite biomass. Proc. Natl. Acad. Sci. USA . May 16 [Epub ahead of print].